Interplay between Ca2+ cycling and mitochondrial permeability transition pores promotes reperfusion-induced injury of cardiac myocytes

Abdallah, Yaser; Kasseckert, Sascha; Iraqi, Wisam; Said, Maher; Shahzad, Tayyab; Erdoğan, Ali; Neuhof, Christiane; Gündüz, Dursun; Schlüter, Klaus‐Dieter; Tillmanns, Harald; Piper, Hans Michael; Reusch, H. Peter; Ladilov, Yury

doi:10.1111/j.1582-4934.2010.01249.x

Cited by 66 publications

(58 citation statements)

References 22 publications

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“…392 There is also close interaction of the sarcoplasmic reticulum with MPTP during reperfusion, and calcium oscillations contribute to MPTP opening and vice versa. [393][394][395] IPC improved sarcoplasmic reticulum function, that is, increased calcium uptake and release along with increased phosphorylation of the ryanodine receptor, sarcoplasmic reticulum ATPase and phospholamban at the end of reperfusion, 396 whereas ryanodine-sensitive calcium release was decreased after the preconditioning cycles in another study, 397 or pharmacological elimination of…”

Section: Sarcoplasmic Reticulummentioning

confidence: 99%

Molecular Basis of Cardioprotection

Heusch

2015

Circulation Research

704

409

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Abstract:Reperfusion is mandatory to salvage ischemic myocardium from infarction, but reperfusion per se contributes to injury and ultimate infarct size. Therefore, cardioprotection beyond that by timely reperfusion is needed to reduce infarct size and improve the prognosis of patients with acute myocardial infarction. The conditioning phenomena provide such cardioprotection, insofar as brief episodes of coronary occlusion/ reperfusion preceding (ischemic preconditioning) or following (ischemic postconditioning) sustained myocardial ischemia with reperfusion reduce infarct size. Even ischemia/reperfusion in organs remote from the heart provides cardioprotection (remote ischemic conditioning). The present review characterizes the signal transduction underlying the conditioning phenomena, including their physical and chemical triggers, intracellular signal transduction, and effector mechanisms, notably in the mitochondria. Cardioprotective signal transduction appears as a highly concerted spatiotemporal program. Although the translation of ischemic postconditioning and remote ischemic conditioning protocols to patients with acute myocardial infarction has been fairly successful, the pharmacological recruitment of cardioprotective signaling has been largely disappointing to date.

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Section: Sarcoplasmic Reticulummentioning

confidence: 99%

Molecular Basis of Cardioprotection

Heusch

2015

Circulation Research

704

409

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“…The concomitant reactivation of the electron transport chain promotes the recovery of J mito (Fig. 3A), which can lead to a hyperpolarization that exceeds pI values in VMs [45]. This enhanced hyperpolarization of J mito can be induced experimentally by H 2 O 2 [46], high glucose, and increased cytosolic Ca 2 + [47] and is followed by mitochondrial depolarization and cell death [33].…”

Section: Reperfusion-induced Ros Production and Its Consequencesmentioning

confidence: 99%

Ischemia/Reperfusion Injury Protection by Mesenchymal Stem Cell Derived Antioxidant Capacity

DeSantiago

Bare

Banach

2013

Stem Cells and Development

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Mesenchymal stem cell (MSC) transplantation after ischemia/reperfusion (I/R) injury reduces infarct size and improves cardiac function. We used mouse ventricular myocytes (VMs) in an in vitro model of I/R to determine the mechanism by which MSCs prevent reperfusion injury by paracrine signaling. Exposure of mouse VMs to an ischemic challenge depolarized their mitochondrial membrane potential (J mito ), increased their diastolic Ca 2 + , and significantly attenuated cell shortening. Reperfusion of VMs with Ctrl tyrode or MSC-conditioned tyrode (ConT) resulted in a transient increase of the Ca 2 + transient amplitudes in all cells. ConT-reperfused cells exhibited a decreased number early after depolarization (EADs) (ConT: 6.3% vs. Ctrl: 28.4%) and prolonged survival (ConT: 58% vs. Ctrl: 33%). J mito rapidly recovered in Ctrl as well as ConT-treated VMs on reperfusion; however, in Ctrl solution, an exaggerated hyperpolarization of J mito was determined that preceded the collapse of J mito . The ability of ConT to attenuate the hyperpolarization of J mito was suppressed on inhibition of the PI3K/Akt signaling pathway or I K,ATP . However, protection of J mito was best mimicked by the reactive oxygen species (ROS) scavenger mitoTEMPO. Analysis of ConT revealed a significant antioxidant capacity that was linked to the presence of extracellular superoxide dismutase (SOD3) in ConT. In conclusion, MSC ConT protects VMs from simulated I/R injury by its SOD3-mediated antioxidant capacity and by delaying the recovery of J mito through Akt-mediated opening of I K,ATP . These changes attenuate reperfusion-induced ROS production and prevent the opening of the permeability transition pore and arrhythmic Ca 2 + release.

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“…MPTP opening is associated with increased mitochondrial ROS generation [45][46][47]. However, MPTP opening has also been reported to regulate mitochondrial ROS production [34][35][36][37][38]. Batandier et al [35] reported that MPTP opening induces a specific conformational change of complex I, and dramatically increases mitochondrial ROS production.…”

Section: Discussionmentioning

confidence: 98%

“…Akopova et al [36] reported that MPTP opening by increasing concentrations of Ca 2þ in the medium results in the increase in mitochondrial ROS production and oxygen consumption. Abdallah et al [37] reported that ischemia reperfusion induced a marked mitochondrial ROS formation in isolated cardiac myocytes. Treatment with the MPTP-inhibitor cyclosporine A prevented the increase in mitochondrial ROS.…”

Section: Discussionmentioning

confidence: 99%

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The role of mitochondrial permeability transition pore in regulating the shedding of the platelet GPIbα ectodomain

Wang¹,

Cai²,

Hu³

et al. 2013

Platelets

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Agonists induce platelet activation or apoptosis with concomitant shedding of the platelet receptor glycoprotein Ibα (GPIbα) ectodomain in a disintegrin and metalloproteinase 17 (ADAM17)-dependent mechanism. Mitochondrial permeability transition pore (MPTP) plays a pivotal role in platelet activation or apoptosis. However, its impact on ADAM17-mediated GPIbα ectodomain shedding remains unclear. Here, we aimed to test the hypothesis that MPTP regulates ADAM17-dependent GPIbα ectodomain shedding. We showed that calcium ionophore A23187- or thrombin plus collagen-induced GPIbα ectodomain shedding was partially inhibited by a MPTP inhibitor, and a MPTP potentiator promoted A23187-induced GPIbα cleavage. Furthermore, A23187-induced elevation of mitochondrial Ca(2+) levels was blocked by the mitochondrial calcium uniporter (MCU) inhibitor Ru360 or treatment with the membrane-permeable Ca(2+) chelator BAPTA-AM. We also demonstrated that an increase in mitochondrial Ca(2+) levels triggered MPTP opening, as revealed by the examination of mitochondrial inner transmembrane potential depolarization. In addition, A23187 induced-mitochondrial reactive oxygen species (ROS) generation was blocked by the MPTP inhibitor or by treatment with the mitochondria-targeted ROS scavenger. Lastly, A23187-induced GPIbα shedding was partially blocked by inhibitors of either ROS or calpain, and was completely inhibited when platelets were exposed to both inhibitors. Therefore, these observations indicate that MPTP opening triggered mitochondrial ROS production, which plays an important role in regulating ADAM17-mediated shedding of the GPIbα ectodomain in A23187-treated platelets.

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Interplay between Ca2+ cycling and mitochondrial permeability transition pores promotes reperfusion-induced injury of cardiac myocytes

Cited by 66 publications

References 22 publications

Molecular Basis of Cardioprotection

Molecular Basis of Cardioprotection

Ischemia/Reperfusion Injury Protection by Mesenchymal Stem Cell Derived Antioxidant Capacity

The role of mitochondrial permeability transition pore in regulating the shedding of the platelet GPIbα ectodomain

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